PROJECT SUMMARY/ABSTRACT The main objective of this R21 grant application is to describe the extent and correlates of inter- individual variability in physical function response to weight loss in older adults with obesity. This project will utilize data collected through the Wake Forest University Claude D. Pepper Older Americans Independence Center (P30 AG021332), representing 1590 overweight or obese older adults who participated in 8 randomized controlled trials of intentional, behavior-based weight loss of 5 to 6 months in duration and completed a comprehensive assessment of physical function (including: objectively measured gait speed, chair rise time, standing balance time and grip strength; and self-reported disability) at baseline and follow-up. Due to the rich characterization of study participants, we will be able to examine whether the observed associations between intentional weight loss and function vary by age, gender, ethnicity, BMI, comorbidity/functional status, body composition, exercise adherence, magnitude of achieved weight loss, inflammatory burden, and/or the metabolomic milieu. The PI's on this project bring complementary experience in aging, nutrition, exercise, and preventive health and Bayesian statistical modeling, along with a track record of high impact publications on weight change, inflammation, and functional decline in older adults. Results will directly enhance our understanding of factors that optimize functional response to weight loss in older adults with obesity, thereby informing the design of future R01 weight loss trials led by the study PIs.